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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00073307




Registration number
NCT00073307
Ethics application status
Date submitted
19/11/2003
Date registered
21/11/2003
Date last updated
6/02/2014

Titles & IDs
Public title
Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer
Scientific title
A Phase III Randomized Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer.
Secondary ID [1] 0 0
11213
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sorafenib (Nexavar, BAY43-9006)
Treatment: Drugs - Placebo

Experimental: Sorafenib (Nexavar, BAY43-9006) - Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Dose modification due to toxicity was permitted.

Placebo comparator: Placebo - Placebo tablets matching in appearance were to be orally administered twice a day.


Treatment: Drugs: Sorafenib (Nexavar, BAY43-9006)
Multi Kinase Inhibitor

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Final Overall Survival (OS) - Primary Analysis in the ITT (Intent To Treat) Population
Timepoint [1] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later
Primary outcome [2] 0 0
Final Overall Survival - Secondary Analysis (Placebo Data Censored at 30June2005) in the ITT Population
Timepoint [2] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later
Secondary outcome [1] 0 0
Final Progression-Free Survival (PFS) - Independent Radiological Review
Timepoint [1] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
Secondary outcome [2] 0 0
Best Overall Response - Independent Radiological Review
Timepoint [2] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
Secondary outcome [3] 0 0
Health-related Quality of Life (HRQOL) by FKSI-10 (Functional Assessment of General Therapy Kidney Symptom Index 10) Assessment
Timepoint [3] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.
Secondary outcome [4] 0 0
Health-related Quality of Life (HRQOL) by Physical Well-Being (PWB) Score of the FACT-G (Functional Assessment of Cancer Therapy-General Version) Assessment
Timepoint [4] 0 0
From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.

Eligibility
Key inclusion criteria
* Patients with unresectable and/or metastatic, measurable renal cell carcinoma histologically or cytologically documented
* Patients must have had one prior systemic therapy for advanced disease, which was completed at least 30 days but no longer than 8 months prior to randomization
* Patients who have at least one uni-dimensional measurable lesion by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)
* Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
* Patients who have adequate coagulation, liver and kidney functions
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with rare subtypes of renal cell carcinoma (RCC) such as pure papillary cell tumors, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors
* Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma,or superficial bladder tumors, or other malignancies curatively treated > 2 years prior to entry
* Cardiac arrhythmias requiring anti-arrhythmics, symptomatic coronary artery disease or ischemia or congestive heart failure
* Patients with a history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Patients with a history or presence of metastatic brain or meningeal tumors
* Patients with seizure disorder requiring medication (such as anti-epileptics)
* History of organ allograft or bone marrow transplant of stem cell rescue
* Patients who are pregnant or breast-feeding Women of childbearing potential must have a negative pregnancy test prior to drug administration. Both men and women enrolled in this trial must use adequate birth control
* Patients who have three or more of the following:

* ECOG performance status greater than or equal to 2,
* Abnormally high lactate dehydrogenase,
* Abnormally high serum hemoglobin,
* Abnormally high corrected serum calcium,
* Absence of prior nephrectomy
* Excluded therapies and medications, previous and concomitant:

* Concurrent anti-cancer chemotherapy, immunotherapy or hormonal therapy except biphosphonates
* Significant surgery with 4 weeks of start of study
* Investigational drug therapy during or within 30 days
* Concomitant treatment with rifampin or St. John's Wort
* Prior use of Raf-kinase inhibitors (RKI), MEK or Farnesyl transferase inhibitors
* Prior use of Bevacizumab, and all other drugs (investigational or licensed) that target VEGF/VEGF receptors

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2010
Sample size
Target
Accrual to date
Final
903
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC
Recruitment hospital [1] 0 0
- Garran
Recruitment hospital [2] 0 0
- Camperdown
Recruitment hospital [3] 0 0
- Liverpool
Recruitment hospital [4] 0 0
- Westmead
Recruitment hospital [5] 0 0
- Heidelberg
Recruitment hospital [6] 0 0
- Wodonga
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
0390 - Wodonga
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Connecticut
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Georgia
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Illinois
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Minnesota
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Missouri
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New York
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Utah
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Virginia
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Washington
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Wisconsin
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Argentina
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Santa Fe
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Argentina
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Capital Federal-Buenos Aires
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Argentina
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Mendoza
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Belgium
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Bruxelles - Brussel
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Brazil
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Parana
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Brazil
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Rio Grande do Sul
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Santiago de Chile
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France
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Bordeaux
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France
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Caen Cedex 5
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Lille Cedex
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France
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Lyon Cedex
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France
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Marseille
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France
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Nantes
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France
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Paris Cedex 15
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France
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Strasbourg
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France
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Toulouse
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France
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Villejuif
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Hamburg
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Hungary
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Budapest
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Debrecen
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Hungary
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Zalaegerszeg
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Israel
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Haifa
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Israel
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Tel Aviv
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Italy
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Milano
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Italy
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Modena
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Italy
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Pavia
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Italy
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Perugia
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Italy
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Reggio Emilia
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Italy
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Roma
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Netherlands
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Nijmegen
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Poland
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Gdansk
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Krakow
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Lodz
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Lublin
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Poznan
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Szczecin
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Warszawa
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Wroclaw
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Russian Federation
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Barnaul
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Russian Federation
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Kazan
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Russian Federation
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Kirov
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Russian Federation
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Moscow
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Russian Federation
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Obninsk
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Russian Federation
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St. Petersburg
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South Africa
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Freestate
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South Africa
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Gauteng
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South Africa
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Kwazulu-Natal
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South Africa
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Western Cape
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Spain
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Bilbao
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Ukraine
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Donetsk
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Ukraine
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Kharkiv
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Ukraine
State/province [86] 0 0
Kiev
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Ukraine
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Lviv
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Ukraine
State/province [88] 0 0
Poltava
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United Kingdom
State/province [89] 0 0
Middlesex
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United Kingdom
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South Glamorgan
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Stratchclyde
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United Kingdom
State/province [92] 0 0
Surrey
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Tyne and Wear
Country [94] 0 0
United Kingdom
State/province [94] 0 0
West Midlands
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Amgen
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate safety, efficacy (including quality of life), and pharmacokinetics of BAY43-9006 when added to Best Supportive Care in patients with unresectable and/or metastatic renal cell cancer, who have received one prior systemic regimen for advanced disease.
Trial website
https://clinicaltrials.gov/study/NCT00073307
Trial related presentations / publications
Antoun S, Birdsell L, Sawyer MB, Venner P, Escudier B, Baracos VE. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol. 2010 Feb 20;28(6):1054-60. doi: 10.1200/JCO.2009.24.9730. Epub 2010 Jan 19.
Bellmunt J, Eisen T, Fishman M, Quinn D. Experience with sorafenib and adverse event management. Crit Rev Oncol Hematol. 2011 Apr;78(1):24-32. doi: 10.1016/j.critrevonc.2010.03.006. Epub 2010 Apr 18.
Massard C, Zonierek J, Gross-Goupil M, Fizazi K, Szczylik C, Escudier B. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol. 2010 May;21(5):1027-31. doi: 10.1093/annonc/mdp411. Epub 2009 Oct 22.
Negrier S, Jager E, Porta C, McDermott D, Moore M, Bellmunt J, Anderson S, Cihon F, Lewis J, Escudier B, Bukowski R. Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET. Med Oncol. 2010 Sep;27(3):899-906. doi: 10.1007/s12032-009-9303-z. Epub 2009 Sep 12.
Pena C, Lathia C, Shan M, Escudier B, Bukowski RM. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: Results from sorafenib phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res. 2010 Oct 1;16(19):4853-63. doi: 10.1158/1078-0432.CCR-09-3343. Epub 2010 Jul 22.
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009 Jul 10;27(20):3312-8. doi: 10.1200/JCO.2008.19.5511. Epub 2009 May 18.
Eisen T, Oudard S, Szczylik C, Gravis G, Heinzer H, Middleton R, Cihon F, Anderson S, Shah S, Bukowski R, Escudier B; TARGET Study Group. Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst. 2008 Oct 15;100(20):1454-63. doi: 10.1093/jnci/djn319. Epub 2008 Oct 7.
Bukowski R, Cella D, Gondek K, Escudier B; Sorafenib TARGETs Clinical Trial Group. Effects of sorafenib on symptoms and quality of life: results from a large randomized placebo-controlled study in renal cancer. Am J Clin Oncol. 2007 Jun;30(3):220-7. doi: 10.1097/01.coc.0000258732.80710.05.
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. doi: 10.1056/NEJMoa060655. Erratum In: N Engl J Med. 2007 Jul 12;357(2):203.
Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM, Liang C, Booth B, Chidambaram N, Morse D, Sridhara R, Garvey P, Justice R, Pazdur R. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006 Dec 15;12(24):7271-8. doi: 10.1158/1078-0432.CCR-06-1249.
Lamuraglia M, Escudier B, Chami L, Schwartz B, Leclere J, Roche A, Lassau N. To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. Eur J Cancer. 2006 Oct;42(15):2472-9. doi: 10.1016/j.ejca.2006.04.023. Epub 2006 Sep 11. Erratum In: Eur J Cancer. 2007 May;43(8):1336.
Quintanilha JCF, Geyer S, Etheridge AS, Racioppi A, Hammond K, Crona DJ, Pena CE, Jacobson SB, Marmorino F, Rossini D, Cremolini C, Sanoff HK, Abou-Alfa GK, Innocenti F. KDR genetic predictor of toxicities induced by sorafenib and regorafenib. Pharmacogenomics J. 2022 Dec;22(5-6):251-257. doi: 10.1038/s41397-022-00279-3. Epub 2022 Apr 28.
Quintanilha JCF, Racioppi A, Wang J, Etheridge AS, Denning S, Pena CE, Skol AD, Crona DJ, Lin D, Innocenti F. PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors. Pharmacogenomics J. 2022 Feb;22(1):82-88. doi: 10.1038/s41397-021-00261-5. Epub 2021 Nov 13. Erratum In: Pharmacogenomics J. 2022 Mar;22(2):145. doi: 10.1038/s41397-021-00264-2.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00073307